Serotonin 5-HT2C receptor is one of the receptors of the biological transmitter serotonin, which is distributed mainly in the central nervous system and controls many physiological functions in vivo. A representative example is the control of appetite. It has been demonstrated in a study using rodents that stimulation of the central serotonin 5-HT2C receptor decreases eating behavior, resulting in decreased body weight. It has also been reported that, in human as well, administration of a serotonin 5-HT2C receptor activator suppresses appetite and decreases body weight (see non-patent document 1). In addition, it has been demonstrated in a at test using a serotonin 5-HT2C receptor activator that stimulation of the central serotonin 5-HT2C receptor suppresses depression-related behaviors (see non-patent document 2), and has also been reported to be effective for many central nervous diseases such as anxiety etc. (see non-patent document 3). The serotonin 5-HT2C receptor is also highly expressed in the parasympathetic nucleus and motorial nerve cell bodies in the sacral spinal cord, and is considered to control the peripheral nervous functions (see non-patent document 4). It has been reported that when a serotonin 5-HT2C receptor activator is administered to rats, penile erection is induced (see non-patent document 5), and urethral resistance is increased (see patent document 1); all these actions are attributed to stimulation of the serotonin 5-HT2C receptor in the sacral spinal cord. For serotonin 5-HT2C receptor activators, many clinical applications are likely, with particular expectations for anti-obesity drugs, anti-depressants, anti-anxiety drugs, therapeutic drugs for male erectile dysfunction, and therapeutic drugs for stress urinary incontinence and the like.
As the pyridooxazepine derivative, the following compounds have been reported.
A compound represented by the formula:
wherein ring Ac is an optionally substituted aromatic ring; ring Bc is a nitrogen-containing 6- to 9-membered ring optionally further having substituent(s) other than -Lc-Rc; Xc is an optionally substituted methylene group; Ar is an optionally substituted aromatic group; Rc is an optionally substituted cyclic group; Lc is an optionally substituted C1-3 alkylene group, —CONH—, —SO2NH— or —SO2—, and Xc is not a methylene group substituted by an oxo group (patent document 2);
a compound represented by the formula:
wherein ring A is an optionally further substituted aromatic heterocycle, ring B is an optionally further substituted nitrogen-containing 6- to 9-membered ring, Xa is an optionally substituted methylene group (excluding—C(═O)—), Xb is an optionally substituted methylene group, Y is an optionally substituted C1-3 alkylene group, —CONH—, —SO2NH— or —SO2—, R is an optionally substituted aromatic group, and ring D is an optionally substituted aromatic ring or an optionally substituted non-aromatic heterocycle, provided that when ring D is an optionally substituted benzene ring, then the benzene ring has a substituent at the ortho-position relative to the bond with ring A, or Xb is a substituted methylene group (patent document 3);a compound represented by the formula:
wherein ring A is a 5- or 6-membered aromatic heterocycle optionally having substituent(s), and ring B is a 7- to 9-membered ring optionally having substituent(s) other than an oxo group wherein the combination of m and n (m,n) is (1,2), (2,1), (2,2), (3,1), (3,2) or (4,1) (patent document 4);a compound represented by the formula:
wherein R1, R2, R3, R4, R5 and R6 are the same or different and each is a hydrogen atom and the like; R7 is monoalkylamino group and the like; R8 is a halogen atom and the like; n is an integer of 0 to 3 (patent document 5).
However, none of these documents report the compound of the present invention.    non-patent document 1: Expert Opinion on Investigational Drugs, 2006, vol. 15, p. 257-266    non-patent document 2: J. Pharmacol. Exp. Ther., 1998, vol. 286, p. 913-924    non-patent document 3: Pharmacology Biochemistry Behavior, 2002, vol. 71, p. 533-554    non-patent document 4: Neuroscience, 1999, vol. 92, p. 1523-1537    non-patent document 5: Eur. J. Pharmacol., 2004, vol. 483, p. 37-43    patent document 1: WO2004/096196    patent document 2: WO2004/067008    patent document 3: JP-A-2006-056881    patent document 4: WO2007/132841    patent document 5: WO2008/108445